Figure 7: CSN6 is overexpressed in many cancer types and correlated with upregulation of Myc target genes.

(a) Transcriptomic analysis revealed frequent CSN6 overexpression in human patients with cancer. Human cancer patient data sets were obtained from the Oncomine database and Gene Expression Omnibus. Data were analysed with Oncomine expression analysis tools and Nexus Expression 2.0. N represents the total number of cancer patients analysed for each cancer type. Only patients with >40% enhancement of CSN6 mRNA level compared with corresponding normal tissues were counted as ‘CSN6 overexpression’. (b) High CSN6 expression correlated with high Myc expression in pancreatic cancer. Pancreatic cancer tissue microarrays were immunostained with anti-CSN6 and anti-Myc. Micrographs of two representative pancreatic cancer specimens are shown (sale bar, 100 μm). (c) CSN6 overexpression correlated with increased levels of Myc target genes in pancreatic cancer patients and breast cancer patients. Human breast cancer patient data sets and pancreatic cancer patient data sets were retrieved from Gene Expression Omnibus (GSE1542, GSE 5847 and GSE2109) and analysed by gene set enrichment (MIT). Oncomine analysis tools and the GSEA program were used to analyse the impact of CSN6 on Myc target gene expression. (d) Enrichment score graphs showed a strong positive enrichment of Myc target gene expression in patients with CSN6-overexpressing pancreatic or breast cancer as described in c. Representative Myc target genes are shown on graphs. Black arrows indicated the position of the corresponding genes on the gene list. P values calculated by the Kolmogorov–Smirnov test and false discovery rates (FDR) are shown below. Abbreviations of genes are given in Supplementary Information. (e) The model shows the CSN6’s positive effect on the expression of representative Myc target genes in human cancers.